The slow rate of extracellular electron transfer (EET) of electroactive microorganisms remains a primary bottleneck that restricts the practical applications of bioelectrochemical systems. ...Intracellular NAD(H/
) (i.e., the total level of NADH and NAD
) is a crucial source of the intracellular electron pool from which intracellular electrons are transferred to extracellular electron acceptors via EET pathways. However, how the total level of intracellular NAD(H/
) impacts the EET rate in Shewanella oneidensis has not been established. Here, we use a modular synthetic biology strategy to redirect metabolic flux towards NAD
biosynthesis via three modules: de novo, salvage, and universal biosynthesis modules in S. oneidensis MR-1. The results demonstrate that an increase in intracellular NAD(H/
) results in the transfer of more electrons from the increased oxidation of the electron donor to the EET pathways of S. oneidensis, thereby enhancing intracellular electron flux and the EET rate.
A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent sodium trifluoromethanesulfinate (NaSO2CF3 or Langlois’ reagent) has been developed incorporating ...a tandem cyclization/dearomatization process. This strategy affords a straightforward route to synthesis of 3‐(trifluoromethyl)‐spiro4.5trienones, and presents an example of difunctionalization of alkynes for simultaneous formation of two carbon–carbon single bonds and one carbon–oxygen double bond.
Spiro mania: A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent NaSO2CF3 has been reported, affording a series of 3‐trifluoromethyl spiro4.5trienones through a tandem cyclization/dearomatization process. In this alkyne difunctionalization process, two carbon–carbon bonds and one carbon–oxygen double bond are simultaneously formed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Betulinic acid is a pentacyclic lupane-type triterpenoid and a potential antiviral and antitumor drug, but the amount of betulinic acid in plants is low and cannot meet the demand for this compound. ...Yarrowia lipolytica, as an oleaginous yeast, is a promising microbial cell factory for the production of highly hydrophobic compounds due to the ability of this organism to accumulate large amounts of lipids that can store hydrophobic products and supply sufficient precursors for terpene synthesis. However, engineering for the heterologous production of betulinic acid and related triterpenoids has not developed as systematically as that for the production of other terpenoids, thus the production of betulinic acid in microbes remains unsatisfactory.
In this study, we applied a multimodular strategy to systematically improve the biosynthesis of betulinic acid and related triterpenoids in Y. lipolytica by engineering four functional modules, namely, the heterogenous CYP/CPR, MVA, acetyl-CoA generation, and redox cofactor supply modules. First, by screening 25 combinations of cytochrome P450 monooxygenases (CYPs) and NADPH-cytochrome P450 reductases (CPRs), each of which originated from 5 different sources, we selected two optimal betulinic acid-producing strains. Then, ERG1, ERG9, and HMG1 in the MVA module were overexpressed in the two strains, which dramatically increased betulinic acid production and resulted in a strain (YLJCC56) that exhibited the highest betulinic acid yield of 51.87 ± 2.77 mg/L. Then, we engineered the redox cofactor supply module by introducing NADPH- or NADH-generating enzymes and the acetyl-CoA generation module by directly overexpressing acetyl-CoA synthases or reinforcing the β-oxidation pathway, which further increased the total triterpenoid yield (the sum of the betulin, betulinic acid, betulinic aldehyde yields). Finally, we engineered these modules in combination, and the total triterpenoid yield reached 204.89 ± 11.56 mg/L (composed of 65.44% betulin, 23.71% betulinic acid and 10.85% betulinic aldehyde) in shake flask cultures.
Here, we systematically engineered Y. lipolytica and achieved, to the best of our knowledge, the highest betulinic acid and total triterpenoid yields reported in microbes. Our study provides a suitable reference for studies on heterologous exploitation of P450 enzymes and manipulation of triterpenoid production in Y. lipolytica.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chronic inflammation induced by persistent microbial infection plays an essential role in tumor progression. Although it is well documented that Epstein-Barr virus (EBV) infection is closely ...associated with nasopharyngeal carcinoma (NPC), how EBV-induced inflammation promotes NPC progression remains largely unknown. Here, we report that tumor infiltration of tumor-associated macrophages (TAM) and expression of CCL18, the cytokine preferentially secreted by TAM, closely correlate with serum EBV infection titers and tumor progression in two cohorts of NPC patients.
compared with EBV
NPC cell lines, EBV
NPC cell lines exhibited superior capacity to attract monocytes and skew them to differentiate to a TAM-like phenotype. Cytokine profiling analysis revealed that NPC cells with active EBV replications recruited monocytes by VEGF and induced TAM by GM-CSF in an NF-κB-dependent manner. Reciprocally, TAM induced epithelial-mesenchymal transition and furthered NF-κB activation of tumor cells by CCL18. In humanized mice, NPC cells with active EBV replications exhibited increased metastasis, and neutralization of CCL18, GM-CSF, and VEGF significantly reduced metastasis. Collectively, our work defines a feed-forward loop between tumor cells and macrophages in NPC, which shows how metastatic potential can evolve concurrently with virus-induced chronic inflammation.
.
•Quorum sensing (QS) systems are widespread in wastewater treatment processes.•QS regulation on waste treatment and electricity harvest were reviewed.•QS manipulation to improve waste treatment and ...energy harvest were summarized.
Cell–cell communication that enables synchronized population behaviors in microbial communities dictates various biological processes. It is of great interest to unveil the underlying mechanisms of fine-tuning cell–cell communication to achieve environmental and energy applications. Pseudomonas is a ubiquitous microbe in environments that had wide applications in bioremediation and bioenergy generation. The quorum sensing (QS, a generic cell-cell communication mechanism) systems of Pseudomonas underlie the aromatics biodegradation, denitrification and electricity harvest. Here, we reviewed the recent progresses of the genetic strategies in engineering QS circuits to improve efficiency of wastewater treatment and the performance of microbial fuel cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
At present, phenolic acid derivatives and triazole derivatives have a good antifungal effect, which has attracted widespread attention. A series of novel phenolic acid triazole derivatives were ...synthesized, and their structures were characterized by IR, MS, NMR, and X-ray crystal diffraction. Compound methyl 4-(2-bromoethoxy)benzoate, methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate, 4-(2-(1H-1,2,4-triazol-1-yl)ethoxy)benzoic acid and 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)-3-methoxybenzoic acid crystallize in the monoclinic system with space group P21/n, the monoclinic system with space group P21, the monoclinic system with space group P21 and the orthorhombic system with space group Pca21, respectively. At a concentration of 100 μg/mL and 200 μg/mL, the antifungal activity against seven plant pathogen fungi was determined. Compound methyl 4-(2-bromoethoxy)benzoate has the best inhibitory effect on Rhizoctonia solani AG1, and the inhibitory rate reached 88.6% at 200 μg/mL. The inhibitory rates of compound methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate against Fusarium moniliforme and Sphaeropsis sapinea at a concentration of 200 μg/mL were 76.1% and 75.4%, respectively, which were better than that of carbendazim.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) has recently been recognized to be one of the risk factors for cardiovascular disease (CVD). However, there is a scarcity of data ...on the relationship between circulating TMAO levels and hypertension in patients with CVD. Meta analysis and a dose-response relationship were used in this study to assess the relationship between circulating trimethylamine N-oxide levels and the risk of hypertension in patients with CVD.
CNKI, Wanfang Database, Pubmed, Embase, Cochrane Library, and Web of Science were searched up to June 01, 2023. Meta-analysis and dose-response analysis of relative risk data from prospective cohort studies reporting on the relationship between circulating TMAO levels and hypertension risk in patients with CVD were conducted.
Fifteen studies with a total of 15,498 patients were included in the present meta-analysis. Compared with a lower circulating TMAO level, a higher TMAO level was associated with a higher risk of hypertension in patients with CVD (RR = 1.14,95%CI (1.08, 1.20)). And the higher the TMAO level, the greater the risk of hypertension. The dose-response analysis revealed a linear dose-response relationship between circulating TMAO levels and the risk of hypertension in patients with CVD. The risk of hypertension increased by 1.014% when the circulating TMAO level increased by 1 μ mol/L.
In patients with CVD, the level of circulating TMAO is significantly related to the risk of hypertension. The risk of hypertension increased by 1.014% for every 1 μ mol/L increase in circulating TMAO levels.
Ethanol extract (EE) from
(PA) is the main ingredient of Kangfuxin, which is a popular traditional chinese medicine (TCM) and has long been used for the clinical treatment of burns, wounds and ...ulcers. We compared the wound-healing activities of three extracts of PA using cutaneous wound-healing in mice as the bioactivity model. These three extracts were EE, total polysaccharide and total protein. We also tracked bioactive fractions in the EE by organic reagent extraction, column chromatography and HPLC. Seven compounds were successfully identified from the water elution fraction of the EE of PA using UPLC-MS. Among these compounds, four compounds (
,
,
,
) were first reported in PA. Some of these compounds have been previously reported to have various pharmacological activities that could contribute to the high wound-healing activity of PA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A BF3·OEt2-AgSCF3 mediated direct trifluoromethylthiolation/cascade cyclization of propynols involving the SCF3 anion nucleophilic pathway is developed. This protocol also provides an opportunity to ...construct valuable trifluoromethylthio-substituted 2H-chromene and 1,2-dihydroquinoline systems with high efficiency under mild conditions. Additionally, the developed BF3·OEt2-AgSCF3 reaction system could be scaled up to gram quantities in a satisfactory yield without inert gas protection.
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IJS, KILJ, NUK, PNG, UL, UM
A novel gram-negative, aerobic, pink, motile, gliding, rod-shaped bacterium, designated P51
T
, was isolated from saline silt samples in Yantai, China. It was able to grow at 4–42 °C (optimum 33 °C), ...pH 4.0–9.0 (optimum 7.0), and in 0–11.0% NaCl (optimum 4.0%, w/v). It grew at 4 °C, which was lower than the minimum temperature for related strains. The genome consisted of 4111 genes with a total length of 5 139 782 bp. The 16S rRNA gene sequence analysis indicated that strain P51
T
was a member of the genus
Echinicola
and most closely related to ‘
Echinicola shivajiensis
’. A genome analysis identified genes encoding proteins associated with carbon source utilisation, and the carotenoid biosynthesis and
β
-lactam resistance pathways. Strain P51
T
shared an average nucleotide identity value below 84.7%, an average amino acid identity value between 70.8 and 89.3%, and a digital DNA-DNA hybridisation identity of between 17.9–28.2% with closely related type strains within the genus
Echinicola
. The sole menaquinone was MK-7, and the major fatty acids were iso-C
15:0
, summed feature 3 (C
16:1
ω
7
c
and/or C
16:1
ω
6
c
), summed feature 4 (anteiso-C
17:1
B and/or iso-C
17:1
I), and summed feature 9 (iso-C
17:1
ω
9
c
and/or 10-methyl C
16:0
). The polar lipids included one phosphatidylethanolamine, one unidentified aminophospholipid, one unidentified phospholipid, three unidentified aminolipids, and one unknown lipid. The phenotypic, chemotaxonomic, and phylogenetic analyses suggest that strain P51
T
is a novel species of the genus
Echinicola
, for which the name
Echinicola salinicaeni
sp. nov. is proposed. The type strain was P51
T
(KCTC 82513
T
= MCCC 1K04413
T
).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ